ZY0511 is a highly selective and potent inhibitor of lysine‐specific histone demethylase 1 (LSD1) with IC50 of 1.7 nM and SPR Kd of 2.42 nM.
ZY0511 strongly inhibitsthe proliferation of a panel of HCC cell lines in a time‐ and concentration‐dependent manner, with IC50 of 0.2-1 uM (144 hours post‐treatment), ZY0511 exhibits stronger efficiency against HCC cells proliferation than SP2509 (Cat. PC-43122).
ZY0511 exhibits high selectivity against 104 cancer‐related kinases, showed no effect against other kinases, including FGFR, VEGFR, and PDGFR, only weakly inhibits ATM, Flt4, ATR/ATRIP, and DNA‐PK with IC50 of 1 uM.
ZY0511 upregulates H3K4me1, H3K4me2, and H3K9me2 in HCC cells.
ZY0511 (100 mg/kg for 18 days, i.p.) inhibits tumor growth in HCC xenograft models, with no observed adverse effect.
ZY0511 modulates the expression of LSD1 downstream genes in HCC cells, upregulates GADD45B expression by inhibiting LSD1 and inducing H3K4me2 in HCC cells.
The combination of ZY0511 and DTP3 (Cat. PC-72696) synergistically inhibits HCC cells proliferation in vitro and in vivo.